Background <p><i>Alisma orientale</i> has traditionally been used to treat internal retention of dampness. Nevertheless, its impact on platelet function remains unclear.</p> Objective <p>This study investigated the antiplatelet effect of <i>A</i>. <i>orientale</i> extract on platelet activation and its biological mechanism of action. Mice were utilized to evaluate <i>A</i>. <i>orientale</i>’s antiplatelet effects through platelet aggregation, granule secretion, and intracellular calcium mobilization. In addition, its antithrombotic effect was assessed through in vivo arterial thrombus formation induced by ferric chloride (FeCl₃). A bleeding time assay was also performed to investigate the hemostatic effect of <i>A</i>. <i>orientale</i>.</p> Results <p>We found that <i>A</i>. <i>orientale</i> treatment significantly suppressed glycoprotein VI (GPVI)-mediated platelet aggregation, granule secretion, and intracellular calcium mobilization. These findings were attributed to <i>A</i>. <i>orientale</i> inhibiting GPVI-mediated platelet signal transduction during cell activation. Moreover, oral administration of <i>A</i>. <i>orientale</i> effectively attenuated FeCl₃-induced arterial thrombus formation without significantly prolonging tail bleeding time.</p> Conclusion <p>These findings suggest that <i>A</i>. <i>orientale</i> may serve as a promising therapeutic candidate for the management of thrombotic disorders.</p>